Hypothesis:

Study Design

Study Design:

Patient Populations:

Patients presenting with an ST-elevation or non–ST-elevation AMI <48 hours after symptom onset were randomized within 5 days after admission.

Exclusions:

Participation in another study, pregnancy, lactation, allergy to roxithromycin or other macrolides, clinically relevant diseases of the liver or the CNS or other systemic diseases that could interfere with adherence to the study protocol, concomitant use of ergotamine- or dihydroergotamine containing drugs, and foreseeable inability to complete the follow-up.

Concomitant Medications:

Principal Findings:

Discontinuation of medication occurred in 18% of patients treated with roxithromycin v. 11% in placebo (p=0.003). 88% of enrolled patients had STEMI.
The trial was discontinued prior to full enrollment due to slow recruitment of patients. There was no significant difference in the primary endpoint of mortality at 12 months (6.5% in the roxithromycin arm vs 6.0% in the placebo arm, p=0.739). There was also no difference in the combined endpoint of death, reinfarction, post-infarction angina, stroke or resuscitation at discharge (18.7% vs 14.1%, p=0.068) or in the combined endpoint of death, reinfarction, unstable angina leading to hospitalization, stroke or resuscitation at 12 months (27.8% v. 23.2%, p=0.110). Use of CABG or PCI by 12 months also did not differ between the 2 arms (56.0% v. 53.3%, p=0.621).

Interpretation:

Among patients with acute MI, treatment with the antibiotic roxithromycin for 6 weeks was not associated with a reduction in mortality at 1 year. Additionally, these data show no immediate or 12 month benefit for the administration of roxithromycin after MI for the composite endpoints. While this trial aimed to enroll 3922 patients, enrollment was halted at 872 patients, due to slow recruitment of patients.
The results of this trial while negative are not generalizable to other antibiotics or other anti-inflammatory agents. Whether differing agents, duration of therapy and follow-up in other patients with atherosclerotic vascular disease will reveal beneficial effects remains to be determined in upcoming larger randomized trials. A recent study by Sander et al suggested that targeting patients with cardiovascular or cerebrovascular disease who were positive for Chlamydia pneumoniae may produce more effective results. The study examined the effect of roxithromycin therapy (150 mg twice daily for 30 days) on the progression of the intima-to-media thickness (IMT) of the common carotid artery using duplex ultrasonography in patients with ischemic stroke over age 55 years. In patients who were positive for Chlamydia pneumoniae, roxithromycin showed a significantly decreased IMT progression after 2 years compared with patients without therapy (0.07 vs 0.11 mm/year, p<0.01). However, in patients who were negative for Chlamydia pneumoniae, there was no difference in IMT progression with vs without use of roxithromycin.